Mechanism of gamma sigma T-cell-mediated inhibition of stem cell differentiation in vitro: possible relevance for myelosuppression in HIV-infected individuals.
We investigated whether gamma delta T cells contribute to the suppression of myelopoiesis in HIV infection. Freshly isolated gamma delta T cells from HIV seropositive patients suppressed CFU-GM growth in vitro. Preactivation of gamma delta T cells with IL-2 and/or IL-15 further reduced the number of CFU-GM. Natural killer cells and to a lower extent CD4+ and CD8+ cells also inhibited CFU-GM growth. In contrast to gamma delta T cells, this effect was not dependent on IL-15 or IL-2 preactivation. Moreover, no enhanced inhibitory effect of CD56+ and CD4+ cells was observed in HIV+ subjects compared to HIV- donors. The myelosuppressive effect of supernatants of gamma delta T cells could be inhibited by antibodies against IFN-gamma or TNF-alpha. Accordingly, we found increased numbers of TNF-alpha or IFN-gamma-secreting CD8+ gamma delta T cells in HIV+ patients. We conclude that the increased fraction of activated gamma delta T cells producing myelosuppressive cytokines might contribute to the dyshematopoiesis frequently observed in HIV-infected individuals.
Dobmeyer
T S
TS
Paul-Ehrlich-Institute, Department of Immunology, Langen, Germany.
Dobmeyer
J M
JM
Klein
S A
SA
Wesch
D
D
Wagner
S
S
Helm
E B
EB
Hoelzer
D
D
Rossol
R
R
Kabelitz
D
D
D002454:Cell Differentiation; D015658:HIV Infections / Q000097:blood*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D019891:Leukopoiesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D019409:Interleukin-15; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma