IL-2 immunotherapy to recently HIV-1 infected adults maintains the numbers of IL-17 expressing CD4+ T (T(H)17) cells in the periphery.
Little is known about the manipulation of IL-17 producing CD4+ T cells (T(H)17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of T(H)17 cells declined, while counts of T(H)17 cells did not change due to an expansion of the CD4+ naïve T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of T(H)17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV-1 Gag.
Ndhlovu
Lishomwa C
LC
Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA. lndhlovu@medsfgh.ucsf.edu
Sinclair
Elizabeth
E
Epling
Lorrie
L
Tan
Qi Xuan
QX
Ho
Terence
T
Jha
Aashish R
AR
Eccles-James
Ijeoma
I
Tincati
Camilla
C
Levy
Jay A
JA
Nixon
Douglas F
DF
Hecht
Frederick M
FM
Barbour
Jason D
JD
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D010750:Phosphoproteins / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D014763:Viral Matrix Proteins / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D044966:Anti-Retroviral Agents; D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D007376:Interleukin-2; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D054301:gag Gene Products, Human Immunodeficiency Virus