HIV-1 preferentially infects CD4+ T helper cells, which play a crucial role in the orchestration of the immune system. The main function of CD4+ T helper cells is to direct and focus immune responses to maximize anti-pathogenic processes, while suppressing non-essential immune responses. In particular, the efficiency of CD4+ T cell help has been strongly associated with the efficacy of virus-specific CD8+ T cell function. Understanding exactly how CD4+ T helper cells coordinate the immune system and respond to immune challenges are likely crucial to the development of an effective HIV vaccine.

Approaches to induce HIV-1-specific CD4+ T cell responses have been met with skepticism thus far as these attempts may expand the pool of HIV-1 specific CD4+ T cells targets.
New studies from our laboratory demonstrate that HIV-1-specific CD4+ T helper responses are able to critically improve HIV-1-specific CD8+ T cells in their functionality but also to successfully inhibit viral replication. These responses are enriched in subjects, who are able to control viral replication and resurrected through antiretroviral therapy.

Our studies are performed in the context of both acute and chronic HIV-1 infection. We therefore examine different group of patients from highly viremic rapid progressors to HIV elite controllers and we also investigate the impact of genetic factors and antiretroviral therapy on HIV-1-specific CD4+ responses.

Much of this work is technically challenging, and requires the creative use of innovative techniques and new technologies.

Present Areas of Investigation:
		Studying CD4 signaling help necessary for inhibition of viral replication by HIV-1 specific CD8+ T cells
		Characterizing CD4 help for specific B-cell responses
		Investigating prospective cytolytic CD4 activity in HIV-1 infection
		Assessing the role of HIV-1-specific CD4+ T cells in the gastrointestinal tract
		Identifying mechanisms which lead to the observed patterns of immunodominance of T cell responses in acute HIV-1 infection

Recent Publications:
		Streeck H, Kwon DS, Pyo A, Flanders M, Chevalier MF, Law K, Jülg B, Trocha K, Jolin JS, Anahtar MN, Lian J, Toth I, Brumme Z, Chang JJ, Caron T, Rodig SJ, Milner DA Jr, Piechoka-Trocha A, Kaufmann DE, Walker BD, Altfeld M. Epithelial adhesion molecules inhibit HIV-1-specific CD8+ T-cell functions. Blood. 2011 Mar 14. PMID: 21403126. Soghoian DZ, Streeck H. Cytolytic CD4(+) T cells in viral immunity. Expert Rev Vaccines. 2010 Dec;9(12):1453-63. Review. PubMed PMID: 21105780; PubMed Central PMCID: PMC3033049.
		International HIV Controllers Study The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science. 2010 Dec 10;330(6010):1551-7. Epub 2010 Nov 4. PubMed PMID: 21051598.
		Chevalier MF, Jülg B, Pyo A, Flanders M, Ranasinghe S, Soghoian DZ, Kwon DS, Rychert J, Lian J, Muller MI, Cutler S, McAndrew E, Jessen H, Pereyra F, Rosenberg ES, Altfeld M, Walker BD, Streeck H. HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function. J Virol. 2011 Jan;85(2):733 41. Epub 2010 Nov 3. PubMed PMID: 21047960; PubMed Central PMCID: PMC3020027.
		Streeck H, Nixon DF. T cell immunity in acute HIV-1 infection. J Infect Dis. 2010 Oct 15;202 Suppl 2:S302-8. Review. PubMed PMID: 20846037; PubMed Central PMCID: PMC2954287.
		Streeck H, Jolin JS, Qi Y, Yassine-Diab B, Johnson RC, Kwon DS, Addo MM, Brumme C, Routy JP, Little S, Jessen HK, Kelleher AD, Hecht FM, Sekaly RP, Rosenberg ES, Walker BD, Carrington M, Altfeld M. Human immunodeficiency virus type 1-specific CD8+ T-cell responses during primary infection are major determinants of the viral set point and loss of CD4+ T cells. J Virol. 2009 Aug;83(15):7641-8
		Meier A, Chang JJ, Chan ES, Pollard RB, Sidhu HK, Kulkarni S, Wen TF, Lindsay RJ, Orellana L, Mildvan D, Bazner S, Streeck H, Alter G, Lifson JD, Carrington M, Bosch RJ, Robbins GK, Altfeld M. Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med. 2009 Aug;15(8):955-9. Epub 2009 Jul 13. PubMed PMID: 19597505; PubMed Central PMCID: PMC2821111.
		Streeck H, Frahm N, Walker BD. The role of IFN-gamma Elispot assay in HIV vaccine research. Nat Protoc. 2009;4(4):461-9. Streeck H, Jessen H, Kuecherer C, Li B, Jessen AB, Dupke S, Baumgarten A, Stahmer I, van Lunzen J, Altfeld M, Walker BD, Allen TM. Epidemiologically linked transmission of HIV-1 illustrates the impact of host genetics on virological outcome. AIDS. 2009 Jan 14;23(2):259-62.
		Streeck H, Li B, Poon AF, Schneidewind A, Gladden AD, Power KA, Daskalakis D, Bazner S, Zuniga R, Brander C, Rosenberg ES, Frost SD, Altfeld M, Allen TM. Immune-driven recombination and loss of control after HIV superinfection. J Exp Med. 2008 Aug 4;205(8):1789-96.
		Streeck H, Brumme ZL, Anastario M, Cohen KW, Jolin JS, Meier A, Brumme CJ, Rosenberg ES, Alter G, Allen TM, Walker BD, Altfeld M. Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells. PLoS Med. 2008 May 6;5(5):e100.
		Streeck H, Cohen KW, Jolin JS, Brockman MA, Meier A, Power KA, Waring MT, Alter G, Altfeld M. Rapid ex vivo isolation and long-term culture of human Th17 cells. J Immunol Methods. 2008 Apr 20;333(1-2):115-25. Streeck H, van Bockel D, Kelleher A. T-cell responses in primary HIV-1 infection. Curr Opin HIV AIDS. 2008 Jan;3(1):52-59.
		Streeck H, Lichterfeld M, Alter G, Meier A, Teigen N, Yassine-Diab B, Sidhu HK, Little S, Kelleher A, Routy JP, Rosenberg ES, Sekaly RP, Walker BD, Altfeld M. Recognition of a defined region within p24 gag by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I alleles. J Virol. 2007 Jul;81(14):7725-31

Major areas of interest include:
		CD4 helper signals for HIV-1-specific CD8+ T cells leading to control of viral replication
		CD4+ Th2 and follicular helper cell induction for the memory development and function of B cell responses in HIV-1 infection;
		cytotoxic potential of CD4+ T-cells in HIV-1 infection since such activity has been described in the control of other viral inactions,
		mechanisms of CD4+ T cell protection from HIV-1 infection,
		role of CD4+ T cells in the gastrointestinal tract (in collaboration with Douglas Kwon)
		and the investigation of possible mechanisms leading to the observed patterns of immunodominance in T cell responses (work in collaboration with the Altfeld lab).