Early increases in superantigen-specific Foxp3+ regulatory T cells during mouse mammary tumor virus infection.
Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Here, we show in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (SAg)-specific Foxp3(+) regulatory T cells (T(reg)) in Peyer's patches (PP). These increases were shown to be dependent on the presence of dendritic cells. CD4(+) CD25(+) T cells from the PP of infected mice preferentially suppress the proliferative response of T cells to SAg-expressing antigen-presenting cells ex vivo. We investigated the influence of the depletion of CD25(+) cells at different stages of the infection. When CD25(+) cells were depleted before MMTV infection, an increase in the number of PP SAg-cognate Foxp3(-) T cells was found at day 6 of infection. Since the SAg response is associated with viral amplification, the possibility exists that T(reg) cells attenuate the increase in viral load at the beginning of the infection. In contrast, depletion of CD25(+) cells once the initial SAg response has developed caused a lower viral load, suggesting that at later stages T(reg) cells may favor viral persistence. Thus, our results indicated that T(reg) cells play an important and complex role during MMTV infection.
Cabrera
Gabriel
G
Instituto de Leucemia Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, División Medicina Experimental, Academia Nacional de Medicina, Pacheco de Melo 3081 (1425), Buenos Aires, Argentina.
Burzyn
Dalia
D
Mundiñano
Juliana
J
Courreges
M Cecilia
MC
Camicia
Gabriela
G
Lorenzo
Daniela
D
Costa
Héctor
H
Ross
Susan R
SR
Nepomnaschy
Irene
I
Piazzon
Isabel
I
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008212:Lymphocyte Depletion; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*; D019562:Viral Load
D000956:Antigens, Viral; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D018089:Superantigens