RESUMEN
Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C+ NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including CD94/NKG2C, CD94/NKG2A, immunoglobulin-like transcript 2 (ILT2, CD85j), KIR2DL1/2DS1, KIR3DL1, and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observations in adults, a positive serology for hCMV was associated with increased numbers of NKG2C+ NK and T cells as well as with ILT2+ T lymphocytes. Moreover, the proportions of CD161+ and NKG2C+CD56-CD3- NK cells also tended to be increased in hCMV+ individuals. Excretion of the virus was associated with higher proportions of NKG2C+ NK cells. Altogether, these data reveal that hCMV may have a profound influence on the NKR repertoire in early childhood.
Asunto(s)
Infecciones por Citomegalovirus/inmunología , Regulación Viral de la Expresión Génica , Células Asesinas Naturales/inmunología , Receptores de Células Asesinas Naturales/biosíntesis , Anticuerpos Antivirales/sangre , Antígenos CD/biosíntesis , Antígenos CD/genética , Niño , Preescolar , Citomegalovirus/inmunología , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/orina , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Lactante , Células Asesinas Naturales/clasificación , Células Asesinas Naturales/metabolismo , Receptor Leucocitario Tipo Inmunoglobulina B1 , Masculino , Subfamilia B de Receptores Similares a Lectina de Células NK/biosíntesis , Subfamilia B de Receptores Similares a Lectina de Células NK/genética , Subfamília C de Receptores Similares a Lectina de Células NK/biosíntesis , Subfamília C de Receptores Similares a Lectina de Células NK/genética , Subfamília D de Receptores Similares a Lectina de las Células NK/biosíntesis , Subfamília D de Receptores Similares a Lectina de las Células NK/genética , Receptores Inmunológicos/biosíntesis , Receptores Inmunológicos/genética , Receptores de Células Asesinas Naturales/genética , Saliva/virología , Orina/virologíaRESUMEN
BACKGROUND: Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection. METHODS: NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays. RESULTS: We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients. CONCLUSION: Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.